Chinese verbal fluency deficiency in temporal lobe epilepsy with and without hippocampal sclerosis: a multiscale study.

To test a Chinese character version of phonemic verbal fluency task in patients with temporal lobe epilepsy (TLE), and assess the verbal fluency deficiency pattern in TLE with and without hippocampal sclerosis. Thirty patients with TLE and hippocampal sclerosis (TLE-HS), 28 patients with TLE and without hippocampal sclerosis (TLE-NHS), and 29 demographically matched healthy controls (HC) participated in this cross-sectional study. Both sexes were enrolled. Participants finished a Chinese character verbal fluency (VFC) task during functional MRI. The activation/deactivation maps, functional connectivity, degree centrality, and community features of left frontal and temporal regions were compared. Neural network classification model was applied to differentiate TLE-HS and TLE-NHS using functional statistics. The VFC scores were correlated with semantic fluency in HC while correlated with phonemic fluency in TLE-NHS. Activation and deactivation deficiency was observed in TLE-HS and TLE-NHS (p < 0.001, k ≥ 10). Functional connectivity, degree centrality, and community features of anterior inferior temporal gyri were impaired in TLE-HS and retained or even enhanced in TLE-NHS (p < 0.05, FDR-corrected). The functional connectivity was correlated with phonemic fluency (p < 0.05, FDR-corrected). The neural network classification reached an area under curve = 0.90 in diagnosing hippocampal sclerosis. The VFC task is a Chinese phonemic verbal fluency task suitable for clinical application in TLE. During the VFC task, functional connectivity of phonemic circuits was impaired in TLE-HS and was enhanced in TLE-NHS, representing a compensative phonemic searching strategy applied by patients with TLE-NHS.Significance Statement Verbal fluency tasks are essential assessment for patients with epilepsy. However, the testing and applying of Chinese phonemic verbal fluency is at an initial stage. We tested a Chinses character verbal fluency task in Chinese with temporal lobe epilepsy, and depicted the functional alteration patterns in them. Our work provided a Chinese verbal fluency task suitable for clinical application. Our results highlighted the importance of left anterior inferior frontal gyrus in Chinese, and might have impact on the surgical protocol of Chinese patients with left TLE and promote further development of rehabilitative and therapeutic approaches for verbal fluency decline.

The clinical and predictive value of 18F-FDG PET/CT metabolic patterns in a clinical Chinese cohort with autoimmune encephalitis.

AIMS: To investigate the diagnostic and predictive role of 18F-FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group. METHODS: Thrty-five patients (20 females and 15 males) with AE were recruited. A voxel-to-voxel semi-quantitative analysis based on SPM12 was used to analyze 18F-FDG PET/CT imaging data compared to healthy controls. Further comparison was made in different prognostic groups categorized by modified Rankin Scale (mRS). RESULTS: In total, 24 patients (68.6%) were tested positive neuronal antibodies in serum and/or CSF. Psychiatric symptoms and seizure attacks were major clinical symptoms. In the acute stage, 13 patients (37.1%) demonstrated abnormal brain MRI results, while 33 (94.3%) presented abnormal metabolism patterns. 18F-FDG PET/CT was more sensitive than MRI (p < 0.05). Patients with AE mainly presented mixed metabolism patterns compared to the matched controls, demonstrating hypermetabolism mainly in the cerebellum, BG, MTL, brainstem, insula, middle frontal gyrus, and relatively hypometabolism in the frontal cortex, occipital cortex, temporal gyrus, right parietal gyrus, left cingulate gyrus (p < 0.05, FWE corrected). After a median follow-up of 26 months, the multivariable analysis identified a decreased level of consciousness as an independent risk factor associated with poor outcome of AE (HR = 3.591, p = 0.016). Meanwhile, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected). CONCLUSION: 18F-FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.

Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research.

Epilepsy, a prevalent neurological disorder characterized by high morbidity, frequent recurrence, and potential drug resistance, profoundly affects millions of people globally. Understanding the microscopic mechanisms underlying seizures is crucial for effective epilepsy treatment, and a thorough understanding of the intricate neural circuits underlying epilepsy is vital for the development of targeted therapies and the enhancement of clinical outcomes. This review begins with an exploration of the historical evolution of techniques used in studying neural circuits related to epilepsy. It then provides an extensive overview of diverse techniques employed in this domain, discussing their fundamental principles, strengths, limitations, as well as their application. Additionally, the synthesis of multiple techniques to unveil the complexity of neural circuits is summarized. Finally, this review also presents targeted drug therapies associated with epileptic neural circuits. By providing a critical assessment of methodologies used in the study of epileptic neural circuits, this review seeks to enhance the understanding of these techniques, stimulate innovative approaches for unraveling epilepsy's complexities, and ultimately facilitate improved treatment and clinical translation for epilepsy.

Clinical features of adult patients with positive NMDAR-IgG coexisting with MOG-IgG.

INTRODUCTION: This study was designed to analyze clinical and radiographic features of adult patients coexisting with NMDAR-IgG and MOG-IgG. METHODS: Eleven adult patients coexisting with NMDAR-IgG and MOG-IgG were collected from Xiangya Hospital, Central South University, between June 2017 and December 2021. Fifty-five patients with anti-NMDAR encephalitis and 49 with MOG-AD were served as controls. RESULTS: Onset age was 27 (IQR 20-34) years old. Seizures and psychotic symptoms were prominent symptoms. Ten of eleven patients presented abnormal T2/FLAIR hyperintensity, mainly involving the cortex, brainstem, and optic nerve. Compared with the NMDAR IgG ( +)/MOG IgG ( -) group, the NMDAR IgG ( +)/MOG IgG ( +) group showed more ataxia symptoms (27.3% vs. 3.6%, P = 0.037), while more T2/FLAIR hyperintensity lesions were found in the brainstem (54.5% vs. 7.3%, P < 0.001) and optic nerve (27.3% vs. 1.8%, P = 0.011) with more abnormal MRI patterns (90.9% vs. 41.8%, P = 0.003). In comparison with the NMDAR IgG ( -)/MOG IgG ( +) group, the NMDAR IgG ( +)/MOG IgG ( +) group had more seizures (72.7% vs. 24.5%, P = 0.007) and mental symptoms (45.5% vs. 0, P < 0.001). The NMDAR IgG ( +)/MOG IgG ( +) group tended to be treated with corticosteroids alone (63.6% vs. 20.0%, P = 0.009), more prone to recur (36.5% vs. 7.3%, P = 0.028) and lower mRS score (P = 0.036) at the last follow-up than pure anti-NMDAR encephalitis. CONCLUSION: The symptoms of the NMDAR IgG ( +)/MOG IgG ( +) group were more similar to anti-NMDAR encephalitis, while MRI patterns overlapped more with MOG-AD. Detecting both NMDAR-IgG and MOG-IgG maybe warranted in patients with atypical encephalitis symptoms and demyelinating lesions in infratentorial regions.

De novo variants in KCNJ3 are associated with early-onset epilepsy.

BACKGROUND: KCNJ3 encodes a subunit of G-protein-coupled inwardly rectifying potassium channels, which are important for cellular excitability and inhibitory neurotransmission. However, the genetic basis of KCNJ3 in epilepsy has not been determined. This study aimed to identify the pathogenic KCNJ3 variants in patients with epilepsy. METHODS: Trio exome sequencing was performed to determine potential variants of epilepsy. Individuals with KCNJ3 variants were recruited for this study. Detailed clinical information and genetic data were obtained and systematically reviewed. Whole-cell patch-clamp recordings were performed to evaluate the functional consequences of the identified variants. RESULTS: Two de novo missense variants (c.998T>C (p.Leu333Ser) and c.938G>A (p. Arg313Gln)) in KCNJ3 were identified in two unrelated families with epilepsy. The variants were absent from the gnomAD database and were assumed to be damaging or probably damaging using multiple bioinformatics tools. They were both located in the C-terminal domain. The amino acid residues were highly conserved among various species. Clinically, the seizures occurred at a young age and were under control after combined treatment. Electrophysiological analysis revealed that the KCNJ3 Leu333Ser and Arg313Gln variants significantly compromised the current activities and exhibited loss-of-function (LOF) effects. CONCLUSION: Our findings suggest that de novo LOF variants in KCNJ3 are associated with early-onset epilepsy. Genetic testing of KCNJ3 in patients with epilepsy may serve as a strategy for precision medicine.

Association between sleep duration and hearing threshold shifts of adults in the United States: National Health and Nutrition Examination Survey, 2015-2016.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to hearing loss (HL). Another sleep characteristics, sleep duration might also be associated with HL, but prior evidence is limited. This study is aimed to investigate the association between sleep duration and hearing level in the adult US population. METHODS: In total, a sample of 2777 individuals aged 20-69 years from the 2015-2016 National Health and Nutrition Examination Survey cycle (NHANES, 2015-2016) were investigated in this study. Self-reported sleep duration data was classified into the short-sleep (< 7 h), normal-sleep (7-9 h), and long-sleep (> 9 h) group. Multivariable linear regression models between sleep duration and hearing threshold shifts were estimated. Interactions between sleep duration and age, gender, race, OSA were also considered, and the study population was stratified by age, gender, race, and OSA to analyze the potential disparities among adults in different subgroups. RESULTS: Long-sleep duration was positively associated with speech- and high-frequency pure-tone average (PTA) thresholds with statistical significance (ß = 1.31, 95%CI: 0.10, 2.53, P = 0.0347, and ß = 2.71, 95%CI: 0.69, 4.74, P = 0.0087, respectively). When stratified by age, short sleep duration was positively associated with low-, and speech-frequency PTAs (P = 0.0140 and 0.0225, respectively) for adults aged 40-59 years, and long-sleep duration was positively associated with low-, and speech-frequency PTAs (P = 0.0495 and 0.0142, respectively) for adults aged 60-69 years with statistical significance. There was statistically significant interaction between OSA and sleep duration on speech-frequency PTA, but no significant interaction between either gender or race with sleep duration on hearing thresholds among US adults. CONCLUSION: Short/long sleep durations are associated with worse hearing level comparing to sleep 7-9 h in the American adults. Nonoptimal sleep duration may be a potential risk factor for HL.

Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND AND AIMS: Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the NOTCH2NLC gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID. METHODS: In this retrospective dual-center study, we reviewed 96 patients with NOTCH2NLC-related NIID, 94 patients with genetically confirmed Charcot-Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 and 2022. RESULTS: Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (n = 27) and non-muscle weakness type (n = 69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC = 0.989, sensitivity = 92.6%, specificity = 97.4%). INTERPRETATION: Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID.

Structural and functional changes of the cerebellum in temporal lobe epilepsy.

Aims: This study aimed to comprehensively explore the cerebellar structural and functional changes in temporal lobe epilepsy (TLE) and its association with clinical information. Methods: The SUIT toolbox was utilized to perform cerebellar volume and diffusion analysis. In addition, we extracted the average diffusion values of cerebellar peduncle tracts to investigate microstructure alterations. Seed-based whole-brain analysis was used to investigate cerebellar-cerebral functional connectivity (FC). Subgroup analyses were performed to identify the cerebellar participation in TLE with/without hippocampal sclerosis (HS)/focal-to-bilateral tonic-clonic seizure (FBTCS) and TLE with different lateralization. Results: TLE showed widespread gray matter atrophy in bilateral crusII, VIIb, VIIIb, left crusI, and left VIIIa. Both voxel and tract analysis observed diffusion abnormalities in cerebellar afferent peduncles. Reduced FC between the right crus II and the left parahippocampal cortex was found in TLE. Additionally, TLE showed increased FCs between left lobules VI-VIII and cortical nodes of the dorsal attention and visual networks. Across all patients, decreased FC was associated with poorer cognitive function, while increased FCs appeared to reflect compensatory effects. The cerebellar structural changes were mainly observed in HS and FBTCS subgroups and were regardless of seizure lateralization, while cerebellar-cerebral FC alterations were similar in all subgroups. Conclusion: TLE exhibited microstructural changes in the cerebellum, mainly related to HS and FBTCS. In addition, altered cerebellar-cerebral functional connectivity is associated with common cognitive alterations in TLE.

CDK4/6 inhibition triggers ICAM1-driven immune response and sensitizes LKB1 mutant lung cancer to immunotherapy.

Liver kinase B1 (LKB1) mutation is prevalent and a driver of resistance to immune checkpoint blockade (ICB) therapy for lung adenocarcinoma. Here leveraging single cell RNA sequencing data, we demonstrate that trafficking and adhesion process of activated T cells are defected in genetically engineered Kras-driven mouse model with Lkb1 conditional knockout. LKB1 mutant cancer cells result in marked suppression of intercellular adhesion molecule-1 (ICAM1). Ectopic expression of Icam1 in Lkb1-deficient tumor increases homing and activation of adoptively transferred SIINFEKL-specific CD8+ T cells, reactivates tumor-effector cell interactions and re-sensitises tumors to ICB. Further discovery proves that CDK4/6 inhibitors upregulate ICAM1 transcription by inhibiting phosphorylation of retinoblastoma protein RB in LKB1 deficient cancer cells. Finally, a tailored combination strategy using CDK4/6 inhibitors and anti-PD-1 antibodies promotes ICAM1-triggered immune response in multiple Lkb1-deficient murine models. Our findings renovate that ICAM1 on tumor cells orchestrates anti-tumor immune response, especially for adaptive immunity.

Integrated Thermofluid Lumped Parameter Model for Analyzing Hemodynamics in Human Fatigue State.

It is well known that driving while fatigued is dangerous and can lead to serious traffic accidents. However, there is a lack of studies on the mechanism of fatigue. This paper sought to infer changes in the cardiovascular system through hand and head skin temperature peripheral factors via an integrated lumped parameter model. A multi-layer inner structure with variable blood perfusion was used to construct a full-body thermal model. The cardiovascular system model provided blood perfusion using lumped parameters. The peripheral resistance and heart rate in the cardiovascular system model were adjusted to match the experimental temperatures of the head and hands obtained from induced fatigue experiments. The simulation results showed that the heart rate and blood pressure decreased, and the peripheral skin resistance of the hands and head increased after fatigue. A decrease in heart rate and an increase in peripheral resistance affect the magnitude of blood flow to the periphery of the body, leading to a decrease in skin temperature during fatigue. The present integrated model elucidates a key effect of human fatigue on the cardiovascular system, which is expected to help improve the accuracy of fatigue monitoring systems.

Cerebellar functional disruption and compensation in mesial temporal lobe epilepsy.

Background: Cerebellar functional alterations are common in patients with mesial temporal lobe epilepsy (MTLE), which contribute to cognitive decline. This study aimed to deepen our knowledge of cerebellar functional alterations in patients with MTLE. Methods: In this study, participants were recruited from an ongoing prospective cohort of 13 patients with left TLE (LTLE), 17 patients with right TLE (RTLE), and 30 healthy controls (HCs). Functional magnetic resonance imaging data were collected during a Chinese verbal fluency task. Group independent component (IC) analysis (group ICA) was applied to segment the cerebellum into six functionally separated networks. Functional connectivity was compared among cerebellar networks, cerebellar activation maps, and the centrality parameters of cerebellar regions. For cerebellar functional profiles with significant differences, we calculated their correlation with clinical features and neuropsychological scores. Result: Compared to HCs and patients with LTLE, patients with RTLE had higher cerebellar functional connectivity between the default mode network (DMN) and the oculomotor network and lower cerebellar functional connectivity from the frontoparietal network (FPN) to the dorsal attention network (DAN) (p < 0.05, false discovery rate- (FDR-) corrected). Cerebellar degree centrality (DC) of the right lobule III was significantly higher in patients with LTLE compared to HC and patients with RTLE (p < 0.05, FDR-corrected). Higher cerebellar functional connectivity between the DMN and the oculomotor network, as well as lower cerebellar degree centrality of the right lobule III, was correlated with worse information test performance. Conclusion: Cerebellar functional profiles were altered in MTLE and correlated with long-term memory in patients.

Shared functional network abnormality in patients with temporal lobe epilepsy and their siblings.

AIM: Temporal lobe epilepsy is a neurological network disease in which genetics played a greater role than previously appreciated. This study aimed to explore shared functional network abnormalities in patients with sporadic temporal lobe epilepsy and their unaffected siblings. METHODS: Fifty-eight patients with sporadic temporal lobe epilepsy, 13 unaffected siblings, and 30 healthy controls participated in this cross-sectional study. We examined the task-based whole-brain functional network topology and the effective functional connectivity between networks identified by group-independent component analysis. RESULTS: We observed increased global efficiency, decreased clustering coefficiency, and decreased small-worldness in patients and siblings (p < 0.05, false discovery rate-corrected). The effective network connectivity from the ventral attention network to the limbic system was impaired (p < 0.001, false discovery rate-corrected). These features had higher prevalence in unaffected siblings than in normal population and was not correlated with disease burden. In addition, topological abnormalities had a high intraclass correlation between patients and their siblings. CONCLUSION: Patients with temporal lobe epilepsy and their unaffected siblings showed shared topological functional disturbance and the effective functional network connectivity impairment. These abnormalities may contribute to the pathogenesis that promotes the susceptibility of seizures and language decline in temporal lobe epilepsy.

Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies-pharmacovigilance database analysis with real-world data validation.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. METHODS: A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. RESULTS: Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05-8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60-184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78-1.04; P = 0.160) and 1.49 (95% CI, 0.95-2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34-50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89-7.92; P = 0.12) and 0.66 (95% CI, 0.03-4.55; P = 0.71), respectively, using ICI monotherapy as reference. CONCLUSIONS: Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

Genetic advances in Meniere Disease.

Meniere Disease (MD) is an idiopathic inner ear disease with complex etiology and pathogenesis, which is still unclear. With the development in gene analysis technology, the genetic research of MD has attracted extensive attention, resulting in a large number of studies on the research of the relationship between human genes and MD. This paper aims to review the studies on this topic in recent years. The studies mainly focused on the genetics of familial MD and the correlation between MD and potentially related functional genes. The results of these studies have demonstrated the complexity and diversity of the pathogenesis of MD with both genetic and epigenetic alterations, suggesting that MD might be related to inflammation, immunity, aqua and ion balance in the lymphatic fluid, virus infection, metabolism, and abnormal function of nerve conduction. The finding of rare mutations in TECTA, MYO7A and OTOG genes and other genes such as CDH23, PCDH15 and ADGRV1 in the same families suggest that the integrity of the stereocilia and their interaction with the tectorial and otolithic membranes could be involved in the pathophysiology of familial MD.

PARP Inhibition Induces Synthetic Lethality and Adaptive Immunity in LKB1-Mutant Lung Cancer.

Contradictory characteristics of elevated mutational burden and a "cold" tumor microenvironment (TME) coexist in liver kinase B1 (LKB1)-mutant non-small cell lung cancers (NSCLC). The molecular basis underlying this paradox and strategies tailored to these historically difficult to treat cancers are lacking. Here, by mapping the single-cell transcriptomic landscape of genetically engineered mouse models with Kras versus Kras/Lkb1-driven lung tumors, we detected impaired tumor-intrinsic IFNγ signaling in Kras/Lkb1-driven tumors that explains the inert immune context. Mechanistic analysis showed that mutant LKB1 led to deficiency in the DNA damage repair process and abnormally activated PARP1. Hyperactivated PARP1 attenuated the IFNγ pathway by physically interacting with and enhancing the poly(ADP-ribosyl)ation of STAT1, compromising its phosphorylation and activation. Abrogation of the PARP1-driven program triggered synthetic lethality in NSCLC on the basis of the LKB1 mutation-mediated DNA repair defect, while also restoring phosphorylated STAT1 to favor an immunologically "hot" TME. Accordingly, PARP1 inhibition restored the disrupted IFNγ signaling and thus mounted an adaptive immune response to synergize with PD-1 blockade in multiple LKB1-deficient murine tumor models. Overall, this study reveals an unexplored interplay between the DNA repair process and adaptive immune response, providing a molecular basis for dual PARP1 and PD-1 inhibition in treating LKB1-mutant NSCLC. SIGNIFICANCE: Targeting PARP exerts dual effects to overcome LKB1 loss-driven immunotherapy resistance through triggering DNA damage and adaptive immunity, providing a rationale for dual PARP and PD-1 inhibition in treating LKB1-mutant lung cancers.

Serum polyunsaturated fatty acids and hearing threshold shifts in adults in the United States: A cross-sectional study.

Background: Few studies have evaluated the association between polyunsaturated fatty acids (PUFAs) and hearing levels. This study aimed to investigate the association between serum PUFAs and hearing threshold shifts in US adults. Methods: We investigated 913 adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Multivariate linear regression analyses were conducted to evaluate associations between PUFA and hearing threshold shifts. Results: Overall, 11 serum PUFAs were inversely associated with low-frequency thresholds, especially in men, and were positively related to high-frequency thresholds, particularly in the 40-59 years old cohort. Furthermore, some serum PUFAs were positively associated with both hearing threshold subgroups in women. Conclusion: Some PUFAs tend to be beneficial for low-frequency hearing status and detrimental to the high-frequency hearing threshold. The male sex may play a protective role in this association, while the female sex and middle age may be detrimental in the effect of PUFAs on hearing function.

Experimental Study of the Propagation Process of Dissection Using an Aortic Silicone Phantom.

BACKGROUND: The mortality of acute aortic dissection (AD) can reach 65~70%. However, it is challenging to follow the progress of AD formation. The purpose of this work was to observe the process of dissection development using a novel tear-embedded silicone phantom. METHODS: Silicone phantoms were fabricated by embedding a torn area and primary tear feature on the inner layer. CT scanning and laser lightening were conducted to observe the variations in thickness and volume of the true lumen (TL) and false lumen (FL) during development. RESULTS: The model with a larger interlayer adhesion damage required a lower pressure to trigger the development of dissection. At the initiation stage of dissection, the volume of TL increased by 25.5%, accompanied by a 19.5% enlargement of tear size. The force analysis based on the change of tear size verified the deduction of the process of interlaminar separation from the earlier studies. CONCLUSIONS: The primary tear and the weakening adhesion of the vessel layers are key factors in AD development, suggesting that some forms of primary damage to the arterial wall, in particular, the lumen morphology of vessels with straight inner lumen, should be considered as early risk predictors of AD.

Genetically proxied gut microbiota, gut metabolites with risk of epilepsy and the subtypes: A bi-directional Mendelian randomization study.

Background: An increasing number of observational studies have revealed an association among the gut microbiota, gut metabolites, and epilepsy. However, this association is easily influenced by confounders such as diet, and the causality of this association remains obscure. Methods: Aiming to explore the causal relationship and ascertain specific gut microbe taxa for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on the genome-wide association study (GWAS) data of epilepsy from the International League Against Epilepsy, with the gut microbiota GWAS results from MiBioGen, and summary-level GWAS data of gut microbiota-dependent metabolites trimethylamine N-oxide and its predecessors. Results: Nine phyla, 15 classes, 19 orders, 30 families, and 96 genera were analyzed. A suggestive association of host-genetic-driven increase in family Veillonellaceae with a higher risk of childhood absence epilepsy (odds ratio [OR]: 1.033, confidential interval [CI]: 1.015-1.051, P IVW = 0.0003), class Melainabacteria with a lower risk of generalized epilepsy with tonic-clonic seizures (OR = 0.986, CI = 0.979-0.994, P IVW = 0.0002), class Betaproteobacteria (OR = 0.958, CI = 0.937-0.979, P IVW = 0.0001), and order Burkholderiales (OR = 0.960, CI = 0.937-0.984, P IVW = 0.0010) with a lower risk of juvenile myoclonic epilepsy were identified after multiple-testing correction. Our sensitivity analysis revealed no evidence of pleiotropy, reverse causality, weak instrument bias, or heterogeneity. Conclusion: This is the first MR analysis to explore the potential causal relationship among the gut microbiota, metabolites, and epilepsy. Four gut microbiota features (two class levels, one order level, and one family level) were identified as potential interventional targets for patients with childhood absence epilepsy, generalized epilepsy with tonic-clonic seizures, and juvenile myoclonic epilepsy. Previous associations in numerous observational studies may had been interfered by confounders. More rigorous studies were needed to ascertain the relationship among the gut microbiota, metabolites, and epilepsy.

Advances in sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is the major cause of premature death in epilepsy patients, particularly those with refractory epilepsy. Sudden unexpected death in epilepsy is thought to be related to peri-ictal cardiac dysfunction, respiratory depression, and autonomic dysfunction, albeit the exact etiology is unknown. Sudden unexpected death in epilepsy prevention remains a huge challenge. The sole presence and frequency of generalized tonic-clonic seizures (GTCS) are the most important risk factors for SUDEP, and nocturnal monitoring may lower the risk with the use of remote listening devices. In addition, studies in animal models of SUDEP have discovered that multiple neurotransmitters, including serotonin (5-HT) and adenosine, may be involved in the pathophysiological mechanisms of SUDEP and that these neurotransmitters could be the targets of future pharmacological intervention for SUDEP. The latest research findings on the epidemiology, clinical risk factors, and probable causes of SUDEP are presented in this review.